p205 is a major target of autoreactive T cells in rheumatoid arthritis

Objective. The p205 autoantigen and interleukin-2 (IL-2) function synergist ically to stimulate T lymphocytes from patients with rheumatoid arthritis ( RA), and a p205-derived amino acid sequence is identical to an immunoglobul in sequence located within a domain that is reactive with rheumatoid factor s (RF), This study was conducted to analyze in detail the T cell immune res ponse against p205 and to investigate whether immunity to p205 may play a r ole in T cell-mediated immunopathology in active RA. Methods. Cibachron blue, protein A-Sepharose, and gel filtration on Sephacr yl were used successively to enrich p205 from synovial fluid (SF), T lympho cytes from RA patients were isolated from the peripheral blood (PB), lymph nodes, and SF, and p205 and peptides derived from known sequences were asse ssed by T cell proliferation assays in the presence of IL-2. Results, P205-specific proliferation of T cells was observed in PB as well as in SF, When p205 was isolated from RA SF, proliferation of RA T cells pe aked on day 3. With p205 purified from SF from trauma patients, there was a significant shift of the maximum T cell proliferation to day 8, T cells we re of CD4 or CD8 phenotype, and B cells did not proliferate to a significan t degree. The T cell response to p205 was always higher for SF mononuclear cells (SFMC) compared with PBMC (P < 0.001), In 1 RA patient who underwent repeated leukapheresis, this led to a reproducible decline in p205-specific T cell proliferation to control levels, PB T cells specifically proliferat ing in response to p205 were detected in 20 of 32 RA patients (63%). Of 26 patients with other inflammatory rheumatic diseases, only 1 showed a minor response to p205, while normal donors did not demonstrate a significant T c ell proliferation. A synthetic p205-derived peptide, with an amino acid seq uence identical to an immunoglobulin sequence located in the area where RF binds, was reactive with T cells from RA patients. Conclusion. P205 appears to be a major target of autoreactive T cells in RA , P205-specific T cells are primed and more abundant at the site of inflamm ation. As a T cell target in RA, p205 may well be an antigen involved in th e initiation of RF production.